Therapeutic implications of SARS-CoV-2 dysregulation of the gut-brain-lung axis

Table 1 Comprehensive list of available gut-based and vagus nerve therapies that could be leveraged to limit the severity of coronavirus disease 19 infection

Therapy	Target	Impact	Clinical outcome
Infliximab[57,58]	TNF-α	Reduced pro-inflammatory response induction and leukocyte migration	Reduced infection rate, symptoms, hospital rate, and mortality
Ustekinumab[57]	IL-12/IL-23	Blocks T cell activation	Possible improved outcome (pooled with other biologics)
Vedolizumab[54,57]	α4β7 integrin	Reduced leukocyte trafficking to gut and associated inflammation	Possible improved outcome (pooled with other biologics)
Corticosteroids[57,58,63]	Glucocorticoid and mineralocorticoid receptors	Reduced inflammatory response	Better or worse clinical outcomes, depending on the timing
Microbiome[176]	Butyrate production	Improved gut barrier integrity and decreased microbial translocation	Reduced inflammatory response
Vitamin D[70,72,74]	Th17 cells	Reduced gut and systemic inflammation	Reduced infection risk and enhanced clinical outcomes
Nicotine and related agonists[142,152,153]	α7nAChR	Reduced Inflammatory Response	Reduced infection rate
Vagus nerve stimulation[151]	α7nAChR	Increased acetylcholine release	Reduced inflammation

TNF-α: Tumor necrosis factor-α; IL: Interleukin; Th17: T helper; nAChR: Nicotinic acetylcholine receptor.